US2002040203A1PendingUtilityA1
Method for transdermal or intradermal delivery of molecules
Priority: Feb 25, 2000Filed: Feb 26, 2001Published: Apr 4, 2002
Est. expiryFeb 25, 2020(expired)· nominal 20-yr term from priority
A61K 9/0009B82Y 5/00A61K 9/127A61N 1/306A61N 1/044A61N 1/0424A61N 1/325
43
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Claims
Abstract
The present invention provides a method for transdermal delivery of molecules. The method comprises the application of electrical pulses concurrently or sequentially with application of the molecules and a lipid composition comprising negatively charged liposomal compositions. The liposomal components are used to enhance permeability of the target site for delivery of the molecule.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A method of enhanced delivery of molecules to or through a delivery site on skin in a subject comprising the steps of:
(a) applying the molecules to be delivered to the delivery site on skin concurrently or sequentially with a liposomal composition comprising negatively charged lipids; (b) applying at least one electric pulse to the delivery site of skin concurrently or sequentially with the molecules and liposomal composition of (a), which are applied concurrently or sequentially with respect to each other, wherein the electric pulse is of sufficient duration and voltage to induce electroporation and delivery of molecules into or through the skin, and wherein the amount of molecule delivered is enhanced in the presence of the liposomal composition as compared to in the absence of the liposomal composition.
2 . The method of claim 1 , wherein the molecules to be delivered are not encapsulated in the liposomal composition.
3 . The method of claim 1 , wherein the negatively charged lipids are phospholipids.
4 . The method of claim 3 , wherein the phospholipids are selected from the group consisting of DOPC and DOPG.
5 . The method of claim 4 , wherein DOPG and DOPC are present in a 1:1 ratio.
6 . The method of claim 1 wherein the at least one electric pulse is applied for a duration of about 10 μsec to about 200 msec.
7 . The method of claim 6 , wherein the electric pulse is applied for a duration of about 1 msec.
8 . The method of claim 1 , wherein the field strength of each pulse is about 0.05 to 5 kV/cm.
9 . The method of claim 1 , wherein the voltage of the electric pulse is about 80 to 200 V.
10 . The method of claim 9 , wherein the number of electric pulses applied is about one to 300.
11 . The method of claim 1 , wherein the molecules are selected from the group consisting of drugs, nucleic acids, peptides, polypeptides, antibodies, immunomodulatory agents, and biological response modifiers.
12 . The method of claim 1 , wherein the molecule to be delivered has an effect selected from the group consisting of therapeutic, preventative, cosmetic, gene therapy and prophylactic.
13 . The method of claim 11 , wherein the molecule to be delivered has an effect selected from the group consisting of therapeutic, preventative, cosmetic, gene therapy and prophylactic.
14 . The method of claim 1 , wherein the molecules, the liposomal composition, and the at least one electric pulse are applied to the delivery site on skin in a delivery mode selected from the group of delivery modes consisting of (a) through (p) in the table:
Apply
molecule-
Apply at
Apply
liposomal
least one
Apply
liposomal
composition
electric
Delivery
molecule
composition
mixture
pulse to
Mode
to skin
to skin
to skin
skin
(a)
1
2
Na
3
(b)
1
3
Na
2,4
(c)
2
3
Na
1
(d)
2
4
Na
1,3,5
(e)
4
2
Na
1,3,5
(f)
3
2
Na
1
(g)
3
1
Na
2,4
(h)
2
1
Na
3
(i)
2
3
Na
1,4
(j)
3
2
Na
1,4
(k)
na
na
1
2
(l)
na
na
2
1
(m)
na
na
2
1,3
(n)
1
1
Na
1
(o)
na
na
1
1
(p)
3
1
na
2
wherein, (i)the numbers 1,2,3,4, 5 indicate the first, second, third, fourth and fifth order of sequential events, (ii) the appearance of the same number in every applicable box indicates concurrent events, (iii) the appearance of a different number(s) in every applicable box indicates the events are sequential, (iv) an event may occur more than once in a delivery mode, and (v) “na” means that event is not applicable.
15 . The method of claim 1 , wherein the at least one electric pulse is delivered using a surface electrode.
16 . The method of claim 14 , wherein the surface electrode is selected from the group consisting of meander, micropatch, caliper and small plate electrodes.
17 . The method of claim 1 , wherein the at least one electric pulse is delivered using an invasive electrode.
18 . The method of claim 16 , wherein the invasive electrode is a microneedle array.
19 . The method of claim 1 , wherein the liposomal composition is a structure selected from the group consisting of liposome, particle, vesicle, microsphere, unilamellar lipid vesicle and multilamellar lipid vesicle.
20 . The method of claim 1 , wherein the liposomal composition is not formed into a structure selected from the group consisting of liposome, particle, vesicle, microsphere, unilamellar lipid vesicle and multilamellar lipid vesicle.
21 . The method of claim 14 , wherein the liposomal composition is a structure selected from the group consisting of liposome, particle, vesicle, microsphere, unilamellar lipid vesicle and multilamellar lipid vesicle.
22 . The method of claim 14 , wherein the liposomal composition is not formed into a structure selected from the group consisting of liposome, particle, vesicle, microsphere, unilamellar lipid vesicle and multilamellar lipid vesicle.
23 . A method of enhanced delivery of molecules to or through a delivery site on skin in a subject comprising the steps of:
(a) applying the molecules to be delivered to the delivery site on skin concurrently or sequentially with a liposomal composition comprising negatively charged phospholipids; (b) applying between one and 60 electric pulses to the delivery site of skin concurrently or sequentially with the molecules and liposomal composition of (a), which are applied concurrently or sequentially with respect to each other, wherein the electric pulse is of a duration of about 10 μsec to about 200 msec and a voltage of about 80 to about 200 V to induce electroporation and delivery of molecules into or through the skin, and wherein the amount of molecule delivered is enhanced in the presence of the liposomal composition as compared to the absence of the liposomal composition.
24 . The method of claim 23 , wherein the molecules to be delivered are not encapsulated in the liposomal composition.
25 . The method of claim 23 , wherein the molecules are selected from the group consisting of drugs, nucleic acids, peptides, polypeptides, antibodies, immunomodulatory agents, and biological response modifiers.
26 . The method of claim 25 , wherein the molecule to be delivered has an effect selected from the group consisting of therapeutic, preventative, cosmetic, gene therapy and prophylactic.
27 . The method of claim 23 , wherein the molecules, the liposomal composition, and the at least one electric pulse are applied to the delivery site on skin in a delivery mode selected from the group of delivery modes consisting of (a) through (p) in the table:
Apply
molecule-
Apply at
Apply
liposomal
least one
Apply
liposomal
composition
electric
Delivery
molecule
composition
mixture
pulse to
Mode
to skin
to skin
to skin
skin
(a)
1
2
Na
3
(b)
1
3
Na
2,4
(c)
2
3
Na
1
(d)
2
4
Na
1,3,5
(e)
4
2
Na
1,3,5
(f)
3
2
Na
1
(g)
3
1
Na
2,4
(h)
2
1
Na
3
(i)
2
3
Na
1,4
(j)
3
2
Na
1,4
(k)
na
Na
1
2
(l)
na
Na
2
1
(m)
na
Na
2
1,3
(n)
1
1
Na
1
(o)
na
Na
1
1
(p)
3
1
na
2
wherein, (i)the numbers 1,2,3,4, 5 indicate the first, second, third, fourth and fifth order of sequential events, (ii) the appearance of the same number in every applicable box indicates concurrent events, (iii) the appearance of a different number(s) in every applicable box indicates the events are sequential, (iv) an event may occur more than once in a delivery mode, and (v) “na” means that event is not applicable.
28 . The method of claim 23 , wherein the at least one electric pulse is delivered using a surface electrode.
29 . The method of claim 28 , wherein the surface electrode is selected from the group consisting of meander, micropatch, caliper and small plate electrodes.
30 . The method of claim 23 , wherein the at least one electric pulse is delivered using an invasive electrode.
31 . The method of claim 30 , wherein the invasive electrode is a microneedle array.
32 . The method of claim 23 , wherein the liposomal composition is a structure selected from the group consisting of liposome, particle, vesicle, microsphere, unilamellar lipid vesicle and multilamellar lipid vesicle.
33 . The method of claim 23 , wherein the liposomal composition is not formed into a structure selected from the group consisting of liposome, particle, vesicle, microsphere, unilamellar lipid vesicle and multilamellar lipid vesicle.
34 . A method of increasing the permeability of the SC layer of the skin comprising applying at least one electric pulse to the SC layer of the skin concurrently or sequentially with application of a liposomal composition comprising negatively charged lipids, wherein the liposomal composition does not encapsulate a molecule to be delivered to the SC layer, and wherein the permeability of the SC layer as measured by the lifetime of pores formed, is higher than in the absence of the liposomal composition.
35 . The method of claim 34 , wherein the electric field strength is from 0.05 to 5 kV/cm.
36 . The method of claim 35 , wherein the pulse duration is from about 10 μsec to about 200 msec.
37 . The method of claim 34 , wherein the negatively charged lipids are phospholipids.
38 . The method of claim 37 , wherein the phospholipids are selected from the group consisting of DOPG and DOPC.
39 . The method of claim 38 , wherein the DOPC and DOPPOG are present in 1:1 ratio.
40 . The method of claim 34 , wherein the liposomal composition is a structure selected from the group consisting of liposome, particle, vesicle, microsphere, unilamellar lipid vesicle and multilamellar lipid vesicle.
41 . The method of claim 34 , wherein the liposomal composition is not formed into a structure selected from the group consisting of liposome, particle, vesicle, microsphere, unilamellar lipid vesicle and multilamellar lipid vesicle.
42 . The method of claim 1 , wherein the negatively charged lipids are free fatty acids.
43 . The method of claim 23 , wherein the negatively charged lipids are free fatty acids.
44 . The method of claim 34 , wherein the negatively charged lipids are free fatty acids.Join the waitlist — get patent alerts
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